We propose a National Cooperative Vaccine Development Group for AIDS comprised of Molecular Vaccines, Inc. (MVI), Albert Einstein School of Medicine, Albany Medical College, and the Laboratory of Viral Diseases, NIAID. This consortium will identify T helper (Th), cytotoxic T cell (Tc) and B cell epitomes of HIV proteins and will develop synthetic peptide or recombinant constructs, varying in their incorporation of individual epitomes, type of epitomes, the number of repeats, and their order in the molecule. These synthetic construct will be compared in standardized assays for neutralization antibody and cytotoxic T cell (CTL) responses in a central core immunology laboratory. The most immunogenic will e used to construct synthetic peptide or recombinant protein molecules which by themselves, inserted into liposome membranes, or expressed in Bacilli Calmette Guerin (BCG) or vaccinia virus vectors will serve as candidate vaccines. Such candidates will be rigorously compared by the core immunology laboratory for induction and boosting of high-titered, BRoadly cross-reactive neutralizing antibody responses, crossreactive CTL responses, and lack of immune restriction. MVI will scale-up promising vaccines under conditions of Good Manufacturing Practice for preclinical safety and primate efficacy studies. This consortium intends to integrate modern immunologic concepts and techniques into established effective, safe, and inexpensive vaccine delivery systems. We believe that such a strategy will markedly increase the chances to develop and use a multivalent, broadly protective vaccine against Human Immunodeficiency Viruses.